This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. HIV encodes for only 15 proteins, but hijacks the use of several human proteins. HIV accessory proteins (Vpu, Vpr, Vif and Nef) form an extensive network of interaction with the human proteins. These interactions allow HIV to manipulate the host cellular environment in a manner that facilitate infection and replication of HIV and downregulation of host defense mechanisms. One of the primary targets for manipulation by HIV is the host ubiquitin-proteasome degradation pathway. HIV-1 Vpu interacts with the multi-subunit Cul1-Roc1-Skp1-bTrCP ubiquitin-ligase complex or the SCF complex and promotes the degradation of CD4 in the endoplasmic reticulum. Vpu forms a ternary complex with the cytoplasmic tail of CD4 and bTrCP, which promotes the ubiquitination and subsequent degradation of CD4. The goal of this project is to determine: a) the structural basis of recognition of Vpu by bTrCP;b) the structural basis of the interaction between CD4 and Vpu;c) the three-dimensional structure of the bTrCP-Vpu-CD4 ternary complex. Mass Spectroscopy analysis will facilitate characterization of protein interaction and identification purified proteins.